PLATELET REACTIONS UNDER CONTROLLED FLUID SHEAR STRESS

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The overall goal of the research is to improve our understanding of reaction kinetics and mechanisms of platelet events of significance in cardiovascular disorders. We subject blood specimens to known, controlled levels of shear stress in a rotational viscometer and determine the response by use of the flow cytometric methods. These studies will be done both in the absence of added agents, and in the presence of platelet agonists and antagonists. Part of the work aims to improve and extend our flow cytometric methodology for studying platelet activation and aggregation in whole blood, and to analyze the results by means of a population balance mathematical model to determine the collision efficiency and breakage rate parameters as functions of biochemical environment, shear rate and shear exposure time. In parallel we will carry out studies using two thrombogenesis models developed by Dr. Ohshima and his colleagues at the University of Tsukuba. Both models use a fluorescent dye-light method of stimulation of thrombus formation, measure platelet thrombus initiation and growth rate, and allow quantitative assessment and control of fluid mechanical shear stress. One model incorporates a cultured endothelial cell monolayer in a cone- plate rotational viscometer. The viscometer applies a known, controlled shear stress to a platelet suspension in contact with the endothelial cell monolayer. A second model measures thrombus initiation and the rate of thrombus growth in blood vessels of rats by use of an intravital microscope-television system.